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followed by surgery. ~ Surgery followed by adjuvant chemotherapy and/or radiotherapy. ~ Chemoradiotherapy (i.e. chemotherapy and radiotherapy given at the same time or sequentially). - The type of treatment – and sometimes the sequence of treatments – offered to patients with resectable Stage III NSCLC will depend on the general health of the patient and any comorbidities, as well as the extent and complexity of the surgery required to remove the tumour. - In unresectable Stage III NSCLC, chemoradiotherapy is the preferred treatment. Alternatively, chemotherapy and radiotherapy can be given sequentially (i.e. one after the other) in patients unable to tolerate concurrent treatment. - Immunotherapy may be offered to some patients with unresectable locally advanced NSCLC following treatment with chemoradiotherapy. • Metastatic (Stage IV) NSCLC - NSCLC is referred to as metastatic or Stage IV disease when it has spread beyond the lung which was initially affected. - It is rarely possible to remove metastatic NSCLC with surgery or to treat it radically with radiotherapy. - Intravenous chemotherapy with a two-drug combination (with or without the addition of the targeted therapy called bevacizumab) is the main treatment for patients with metastatic NSCLC. - The choice of drugs used will largely depend on the general health of the patient and the histological subtype of the tumour. 6 Non-small-cell lung cancer - Patients whose tumours express relatively high levels of programmed death-ligand 1 (PD-L1) protein (determined by molecular testing using a tumour biopsy) may receive first-line immunotherapy with pembrolizumab. - Patients whose tumours contain specific mutations (alterations) to the epidermal growth factor receptor (EGFR), BRAF, anaplastic lymphoma kinase (ALK) or ROS1 genes (determined by molecular testing using a tumour biopsy) are best treated with oral targeted therapies given continuously. - After 4–6 cycles of doublet chemotherapy (i.e. two chemotherapy drugs given together), maintenance treatment (treatment to help keep the cancer from coming back) with a chemotherapy drug called pemetrexed, may be given to patients in good general health. The targeted therapy erlotinib may be offered as maintenance treatment in patients whose tumours have EGFR mutations. - Should the cancer come back (relapse or recurrence), second- and third-line treatments may be offered. Suitable second- and third-line treatments depend on which first-line treatment has been received and on the general health of the patient. Treatment options include: chemotherapy (pemetrexed or docetaxel), immunotherapy (nivolumab, pembrolizumab or atezolizumab), when not given as first-line treatment, antiangiogenic therapy (nintedanib or ramucirumab) in combination with docetaxel, and targeted therapies (afatinib, gefitinib, erlotinib, osimertinib, dabrafenib in combination with trametinib, crizotinib, ceritinib, alectinib, brigatinib or lorlatinib) for patients with molecular alterations. ~ Patients whose tumours have EGFR mutations who have received first-line treatment with erlotinib, gefitinib or afatinib, and who have a confirmed EGFR T790M mutation, may be subsequently treated with osimertinib. ~ Patients with a confirmed BRAF mutation who have received first-line treatment with dabrafenib and trametinib may receive second-line platinum-based chemotherapy. ~ Patients whose tumours have ALK rearrangements and who have received first-line treatment with crizotinib may be treated with second-line ceritinib, alectinib, brigatinib or lorlatinib if available. Follow-up after treatment • Patients who have completed treatment for Stage I–III NSCLC are typically followed-up with clinical and radiological examinations every 6 months for the first 2 years and annually after that. • Patients who have completed treatment for metastatic disease are typically followed up with radiological examinations every 6–12 weeks (depending on their suitability for further treatment) so that second-line therapy can be started if needed. 7 ESMO Patients Guide Anatomy of the lungs The lungs form part of our respiratory (breathing) system, which includes: • Nose and mouth. • Trachea
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